DESCRIPTION: Automated, image-based screening (high content screening or HCS) of cell populations continues to be developed and exploited as a means to characterize and measure the phenotypic responses of primary and established cell lines that represent either a normal or a disease state. This screening paradigm has had significant impact on our ability to identify key proteins and pathways in biological processes and disease using both genome-wide RNAi libraries and small molecule libraries, the latter providing both chemical probes to further our understanding of biology and potential chemical leads for pre-clinical drug development. In both regimes, image-based screens can offer a much richer quantitative assessment of cellular phenotypes than the whole-well, endpoint assays used in traditional high throughput screening (HTS). Consequently, this approach has significant potential to aid our understanding of the mechanisms of disease and to improve the success rate of drug discovery efforts. The U. T. Southwestern Medical Center purchased a Bectin-Dickinson (BD) Pathways 855 automated HCS system in 2008. This was the first such system purchased in the Dallas/Fort Worth metroplex. Since its implementation, interest in HCS screens here has exceeded the capacity of this instrument such that we are severely limited in our ability to conduct library screens and develop assays for future screens in parallel. Much of this relates to the instrument's limitations for throughput. Unfortunately, BD has decided to discontinue this instrument and therefore has no plans to make improvements or offer upgrades. We propose the purchase of a state-of-the-art HCS platform such that we can meet the demands of large chemical and genome-wide RNA screens while satisfying the needs for assay development and hit follow up. This new platform will ultimately allow us to retire the BD Pathway 855 system when support ends from BD.